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NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

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Page 1: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

NYU Medical CenterDepartment of Medicine

Clinical Pathological ConferenceJanuary 18, 2008

Page 2: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Chief Complaint

• 77 year-old man with acute breathlessness and productive cough for eight days

Page 3: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

History of Present Illness

• 50 years PTA – patient started smoking 2 packs of cigarettes daily and consumed 1 quart of alcohol daily x 40 years

– diagnosed with hypertension

• 6 years PTA – intermittent hematuria

– Cystoscopy with bladder biopsies showed bladder diverticulum, no malignancy

• 1 year PTA – developed breathlessness which worsened with exertion but did not seek medical attention

Page 4: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

History of Present Illness (cont)

• ~4 weeks PTA:– Developed cough, CXR was reported as normal

• 12 days PTA:– Admitted to an outside hospital with 3 days of gross

hematuria and flank tenderness – CXR showed bilateral lower lung field infiltrates and

bilateral pulmonary nodules

• At outside hospital:– Treated for Enterococcus UTI– Abdominal CT scan negative for LAN,

hydronephrosis, urothlithiasis or other pelvic abnormalities

Page 5: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

History of Present Illness (cont)

• 8 days PTA:– Developed acute breathlessness, chest

tightness, productive cough– Empirically treated for pneumonia– Chest CT – multiple pulmonary nodules and

small bilateral pleural effusions– Sputa negative for AFB smear (3 samples)

Page 6: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

History of Present Illness (cont)

• 4 days PTA:– Bronchoscopy was performed, BAL negative

for AFB, positive for Candida albicans– Transbronchial biopsy of lower lung

parenchyma – focal hemorrhage and small lymphocytic infiltration; rare single large atypical cells and macrophages

– Gomori methenamine silver and gram stain – small intracellular material in macrophages

Page 7: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

History of Present Illness (cont)

• The patient’s respiratory status slowly declined over the following 4 days

• He was transferred to the NY Harbor VA hospital for further workup

• A procedure was perfomed

Page 8: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Further History

• Past Medical History– BPH, PUD, diverticulosis, essential tremor

• Past Surgical History– Multiple hernia repairs, exploratory laparotomy

• No allergies• Medications

– Piperacillin/tazobactam, azithromycin, atenolol, ipratropium, albuterol, tylenol with codeine, primidone, finasteride, terazosin

Page 9: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Further History (cont)

• Family history– Mother and Brother with coronary artery disease;

Sister with cancer of unknown primary

• Social history– Born in the US, lived with his wife, retired

maintenance worker– Korean War veteran– 80 pack years tobacco use; 40 years alcohol abuse– No illicit drug use

• Review of systems– Otherwise negative

Page 10: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Physical Exam• Elderly man lying in bed in respiratory distress

but able to answer questions• T 100.5ºF, HR 103 bpm, BP 103/56mmHg• RR 22-26/min, SaO2 85-95% on 100% O2• Bibasilar crackles• Tachycardic• Obese abdomen

• Otherwise exam was normal

Page 11: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Laboratory Data

134

4.3

99

25

9

0.9

145

25

31

390.6

0.2

4.7

2.3

16.2 34.8

1.3

11.4 237

14.6

42.3

87N 5L 6M 0E

MCV 93

RDW 13

Troponin 0.38ng/mL (0.03 to 0.09) CPK 69 IU/L (38-174)ESR 27mm/60min (0 to 15) LDH 233 U/L (91-180)Legionella urine antigen negative

Page 12: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Admission ECG

Sinus tachycardia, rate 109 bpm, normal axis, normal intervals, otherwise normal ECG

Page 13: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Further Data

• Transthoracic Echocardiogram– Normal left ventricular size– Ejection fraction normal (70%)– Right atrium and ventricle normal size– Pulmonary artery pressure normal– No vegetations

Page 14: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Medical Student Presenters

• Histoplasmosis: Allison Chatalbash

• Legionnaires’ disease: Alexis Rodriguez

• Renal cell carcinoma: Yelena Shusterman

• Wegener’s granulomatosis: Daniel Smith

Page 15: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Radiology

Dr. Maria Shiau

Page 16: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Baseline chest radiograph –2/11/05, 2 weeks PTA to outside hospital

Page 17: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Admission chest radiograph (outside hospital) on 2/28/05

Page 18: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Chest radiograph – hospital day 13 (NY Harbor VA day 1) on 3/8/05

Page 19: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Chest computed tomography scan – 3/8/05

Page 20: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Chest computed tomography scan – 3/8/05

Page 21: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Chest computed tomography scan – 3/8/05

Page 22: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Chest computed tomography scan – 3/8/05

Page 23: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Chest computed tomography scan – 3/8/05

Page 24: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Consultant

Dr. David Chong

Page 25: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Pathology

Dr. Rosemary Wieczorek

Page 26: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

H&E stain

Page 27: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Beta HCG stain

Page 28: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Electron Microscopy – Rough ER

Page 29: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Electron Microscopy – Glycogen

Page 30: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Additional Images

Dr. Maria Shiau

Page 31: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Amyloid

Page 32: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Metastatic Melanoma

Page 33: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Wegner’s

Granulomatosis

Page 34: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Wegner’s

Granulomatosis

Page 35: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Aspergillosis

Page 36: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Lymphoma

Page 37: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

lymphoma

Page 38: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Final Diagnosis:

Extragonadal Mixed Germ Cell Tumor

(choriocarcinoma plus seminoma)

Page 39: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Extragonadal Germ Cell Tumors(EGGCT)

• Represent only 1 to 5% of all GCTs

• Usually arise from a midline point of origin:– Anterior mediastinum (50-70%)

– Retroperitoneum (30-40%)

– Pineal gland (5%)

– Sacrococcyx (<5%)

• May also represent metastasis of occult carcinoma in situ (CIS) in the gonad with reverse migration

• Genetically similar to primary gonadal tumors

Page 40: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Types of Germ Cell Tumors

• Seminomas (30-40%)or

• Nonseminomas (60-70%)

– Yolk sac – Embryonal carcinoma – Choriocarcinomas– Teratomas– Nonteratomatous combined GCTs

Page 41: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Mediastinal Germ Cell Tumors• Most common site of EGGCTs, either mature teratomas

(60-70%) or malignant (30-40%)• Malignant MGCTs = seminomas (40%) or nonseminomas

(60%)

• Symptoms include:• chest pain dyspnea

• superior vena cava syndrome cough

• postobstructive pneumoniafever / weight loss

• Dysphagia shoulder pain

• vocal cord paralysis hoarseness

• Metastases to local lymph nodes or to distant sites, such as the lungs, liver, or bone, may be present in 20-50% of cases on presentation

Page 42: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Extragonadal Germ Cell Tumors

• Pulmonary parenchyma is a rare primary site

• Prognosis depends on histology and location of primary site– Overall 5-year survival: 40-65% – Best survival rates with extragonadal seminomas

Page 43: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Laboratory Studies• Human chorionic gonadotropin (bhCG)

– Elevated in choriocarcinoma and embryonal carcinoma

– Prostate, bladder, ureteral, and renal carcinomas

• Alpha fetoprotein (AFP)– Elevated in yolk sac and embyronal carcinoma– NOT produced by pure seminomas or pure

choriocarcinomas– Pregnancy, hepatocellular carcinoma, cirrhosis,

hepatitis

• LDH – nonspecific, correlates with tumor burden

Page 44: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Imaging• Testicular Ultrasound

– Helps to exclude gonadal primary tumor

• Computed tomography (CT)– Mature teratomas: heterogeneous, cystic, well-

defined anterior mediastinal masses +/- calcifications

– Seminoma MGCT: bulky, lobulated, homogeneous anterior mediastinal masses, calcification rare

– Nonseminoma MGCT: irregular anterior mediastinal masses with low attenuation and adjacent organ involvement

Page 45: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Treatment

• Mediastinal GCTs:– Seminomas: Cisplatin-based chemotherapy

• Bleomycin, etoposide, cisplatin (BEP) x 4 cycles

– Nonseminomas: chemotherapy followed by surgical excision of residual masses

Page 46: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

GonadalCarcinoma In Situ

Misplaced primordialgerm cell in lung

Malignant transformation

Increased lungtumor burden

Pulmonary nodulesPleural effusion

Pulmonary infiltrates

Local inflammation and/orinfection

Fever, tachycardia

Elevated WBCNeutrophilia

Elevated LDH

BreathlessnessChest tightness

Cough

Elevated ESR

Lung crackles

Hypoxia

Reverse migration

Page 47: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Patient Follow-up

• Hospital Day #1 (total hospital day 13)– Amphotericin was started for fungal coverage and

antibacterials were stopped– Repeat chest CT showed multiple pulmonary nodules

and bilateral pleural effusions

• Hospital Day #2– Open lung biopsy was performed

• Pleural fluid: 9 WBC (59% segs, 29% lymphs, 12% macrophages), 70,000 RBC, no malignant cells

– HIV test negative– NSTEMI post-procedure

Page 48: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Patient Follow-up• Hospital Day #3

– Pathology c/w metastatic carcinoma, poorly-differentiated (favored adenocarcinoma)

– Amphotericin was discontinued

• Hospital Days #4-6– Oncology work-up was initiated with repeat physical

exam– Left testicle noted to be larger in size than right side but

without nodule– Urine beta-hCG positive– Quantitative HCG 2318 mIU/ml (0 to 5)– Alpha-fetoprotein negative– Scrotal U/S showed hydrocele but no testicular mass

Page 49: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Patient Follow-up

• Hospital Days #6-9– Clinical status deteriorated– Immunopathology positive for HCG, but AFP negative– Consistent with mixed germ cell tumor composed of

choriocarcinoma and seminoma

• Hospital Days #10-20– Started chemotherapy with cisplatin-based regimen for

five days– No improvement in hypoxemia or radiographic findings– Progressive multiorgan failure– The patient expired one week after completing

chemotherapy

Page 50: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

References

Malagon HD et al. Germ cell tumors with sarcomatous components: a clinicopathologic and immunohistochemical study of 46 cases. Am J Surg Pathol 2007.Sep;31(9):1356-62.

Parada D et al. Extragonadal retroperitoneal germ cell tumor: primary versus mestastes? Arch Esp Urol 2007. Jul-Aug;60(6):713-19.

Robertson JH. An unusual tumor presentation. Int Surg 2007. Jul-Aug;93(4):218-20.

Laroira ST et al. Unusual presentations of germ cell tumors: nonseminomatous extragonadal germ cell tumor presenting with pulmonary emboli. J Clin Onc 2001. 19(3):915-6.

Makhoul I et al. Extragonadal germ cell tumors. http://www.emedicine.com/MED/topic759.htm. June 2004.

Page 51: NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

Acknowledgements

• Dr. Robert Smith

• Dr. David Chong

• Dr. Maria Shiau

• Dr. Rosemary Wieczorek